Intrexon, ZIOPHARM unite against graft-versus- host disease

GERMANTOWN, M.D. & BOSTON—Synthetic biology company Intrexon Corp. and ZIOPHARM Oncology Inc., a biopharmaceutical company specializing in new cancer immunotherapies, have announced the formation of an exclusive channel collaboration (ECC) for the treatment and prevention of graft-versus-host disease (GvHD), one of the leading complications of organ and allogeneic hematopoietic stem-cell transplantation (HSCT) that can seriously impair the quality of life and survival of patients. The terms of the agreement stipulate that ZIOPHARM will pay Intrexon a technology access fee of $10 million in cash, as well as reimbursement for all research and development costs. In addition, the deal provides for equal sharing of operating profits.

The focus for this deal will be to address the underlying pathologies of GvHD through engineered cell platforms to express and deliver interleukin-2 (IL-2), a cytokine that is critical for the modulation of the immune system. Via the ECC, Intrexon and ZIOPHARM will pursue engineered cell therapy strategies—used separately or together—for the targeted treatment of GvHD. The first approach will be infusion of regulatory T cells that conditionally express IL-2 utilizing Intrexon's proprietary gene control approaches, such as its RheoSwitch platform. The second tactic is deploying orally delivered microbe-based ActoBiotics therapeutics that express IL-2 to modulate immune function.

Dr. Samuel Broder, senior vice president and head of Intrexon's Health Sector, said, “GvHD substantially impairs the quality of life and survival of transplant patients. We believe adoptive therapy with gene-modified T cells may offer an exciting alternative approach for restoring 'immune homeostasis' and countering the destructive pro-inflammatory mediators of GvHD. This ECC also includes access to the ActoBiotics platform as an innovative approach to GvHD.”

The ECC will seek to expand on the benefits of IL-2 immunotherapy under Intrexon's tech to develop clinical-grade regulatory T cells that can precisely deliver IL-2, with the ActoBiotics platform used to help target delivery of IL-2 directly to the digestive tract.

As described on Intrexon's website, the ActoBiotics platform enables the creation of orally delivered biopharmaceuticals. Specifically, “food-grade microbes (Lactococcus lactis) are engineered to generate biologically contained ActoBiotics therapeutics for in-situ expression and secretion of novel proteins and peptides including cytokines, enzymes, hormones and monoclonal antibodies within the body. The ActoBiotics platform offers the unique ability to deliver biological effectors selectively to the oral and gastrointestinal tract enabling treatment opportunities not achievable through customary mechanisms like injectable medicines and permitting ease of administration for patients.”

The company's RheoSwitch technology “delivers precise rheostatic control and optimizes performance in multiple biological systems (human, animal, yeast and plant) for a diverse range of applications, including gene therapy, biotherapeutics and agriculture. The RheoSwitch Therapeutic System offers transcriptional control of a wide variety of therapeutic genes by regulating the timing and dose of an oral activator ligand.”

“The combined expertise and the knowledge gained from our current research programs with Intrexon in adoptive T cell therapies and cytokine modulation for treatment of cancer, position us well to develop and implement therapeutic approaches addressing an area of high unmet medical need for patients with GvHD,” Dr. Laurence Cooper, CEO of ZIOPHARM, remarked in a press release.

Allogeneic HSCT is used to treat a number of diseases, including hematological malignancies, immunological deficiencies and some non-malignant conditions. Roughly 40 to 60 percent of patients undergoing HSCT develop either acute or chronic GvHD. Immunosuppressive agents and systemic steroids, which are commonly used to combat GvHD, can be toxic and have limited efficacy. However, human studies featuring low-dose subcutaneous IL-2 in patients with steroid-refractory GvHD have shown the treatment to act via regulatory T cells to ameliorate the expression of GvHD.